Do orthopaedic shoes improve local dynamic stability of gait? An observational study in patients with chronic foot and ankle injuries.

BACKGROUND: Complex foot and ankle fractures, such as calcaneum fractures or Lisfranc dislocations, are often associated with a poor outcome, especially in terms of gait capacity. Indeed, degenerative changes often lead to chronic pain and chronic functional limitations. Prescription footwear represents an important therapeutic tool during the rehabilitation process. Local Dynamic Stability (LDS) is the ability of locomotor system to maintain continuous walking by accommodating small perturbations that occur naturally during walking. Because it reflects the degree of control over the gait, LDS has been advocated as a relevant indicator for evaluating different conditions and pathologies. The aim of this study was to analyze changes in LDS induced by orthopaedic shoes in patients with persistent foot and ankle injuries. We hypothesised that footwear adaptation might help patients to improve gait control, which could lead to higher LDS: METHODS: Twenty-five middle-aged inpatients (5 females, 20 males) participated in the study. They were treated for chronic post-traumatic disabilities following ankle and/or foot fractures in a Swiss rehabilitation clinic. During their stay, included inpatients received orthopaedic shoes with custom-made orthoses (insoles). They performed two 30s walking trials with standard shoes and two 30s trials with orthopaedic shoes. A triaxial motion sensor recorded 3D accelerations at the lower back level. LDS was assessed by computing divergence exponents in the acceleration signals (maximal Lyapunov exponents). Pain was evaluated with Visual Analogue Scale (VAS). LDS and pain differences between the trials with standard shoes and the trials with orthopaedic shoes were assessed. RESULTS: Orthopaedic shoes significantly improved LDS in the three axes (medio-lateral: 10% relative change, paired t-test p < 0.001; vertical: 9%, p = 0.03; antero-posterior: 7%, p = 0.04). A significant decrease in pain level (VAS score -29%) was observed. CONCLUSIONS: Footwear adaptation led to pain relief and to improved foot & ankle proprioception. It is likely that that enhancement allows patients to better control foot placement. As a result, higher dynamic stability has been observed. LDS seems therefore a valuable index that could be used in early evaluation of footwear outcome in clinical settings.

Effectiveness of chronic obstructive pulmonary disease-management programs: systematic review and meta-analysis

BACKGROUND: Disease-management programs may enhance the quality of care provided to patients with chronic diseases, such as chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to assess the effectiveness of COPD disease-management programs. METHODS: We conducted a computerized search of MEDLINE, EMBASE, CINAHL, PsychINFO, and the Cochrane Library (CENTRAL) for studies evaluating interventions meeting our operational definition of disease management: patient education, 2 or more different intervention components, 2 or more health care professionals actively involved in patients' care, and intervention lasting 12 months or more. Programs conducted in hospital only and those targeting patients receiving palliative care were excluded. Two reviewers evaluated 12,749 titles and fully reviewed 139 articles; among these, data from 13 studies were included and extracted. Clinical outcomes considered were all-cause mortality, lung function, exercise capacity (walking distance), health-related quality of life, symptoms, COPD exacerbations, and health care use. A meta-analysis of exercise capacity and all-cause mortality was performed using random-effects models. RESULTS: The studies included were 9 randomized controlled trials, 1 controlled trial, and 3 uncontrolled before-after trials. Results indicate that the disease-management programs studied significantly improved exercise capacity (32.2 m, 95% confidence interval [CI], 4.1-60.3), decreased risk of hospitalization, and moderately improved health-related quality of life. All-cause mortality did not differ between groups (pooled odds ratio 0.84, 95% CI, 0.54-1.40). CONCLUSION: COPD disease-management programs modestly improved exercise capacity, health-related quality of life, and hospital admissions, but not all-cause mortality. Future studies should explore the specific elements or characteristics of these programs that bring the greatest benefit.

Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia.

Background Geleophysic dysplasia (GD, OMIM 231050) is an autosomal recessive disorder characterised by short stature, small hands and feet, stiff joints, and thick skin. Patients often present with a progressive cardiac valvular disease which can lead to an early death. In a previous study including six GD families, we have mapped the disease gene on chromosome 9q34.2 and identified mutations in the A Disintegrin And Metalloproteinase with Thrombospondin repeats-like 2 gene (ADAMTSL2). Methods Following this study, we have collected the samples of 30 additional GD families, including 33 patients and identified ADAMTSL2 mutations in 14/33 patients, comprising 13 novel mutations. The absence of mutation in 19 patients prompted us to compare the two groups of GD patients, namely group 1, patients with ADAMTSL2 mutations (n=20, also including the 6 patients from our previous study), and group 2, patients without ADAMTSL2 mutations (n=19). Results The main discriminating features were facial dysmorphism and tip-toe walking, which were almost constantly observed in group 1. No differences were found concerning heart involvement, skin thickness, recurrent respiratory and ear infections, bronchopulmonary insufficiency, laryngo-tracheal stenosis, deafness, and radiographic features. Conclusions It is concluded that GD is a genetically heterogeneous condition. Ongoing studies will hopefully lead to the identification of another disease gene.

Epidemiology of pulmonary hypertension: new data from the Swiss registry.

since 1999 data from pulmonary hypertension (PH) patients from all PH centres in Switzerland were prospectively collected. We analyse the epidemiological aspects of these data. PH was defined as a mean pulmonary artery pressure of >25 mm Hg at rest or >30 mm Hg during exercise. Patients with pulmonary arterial hypertension (PAH), PH associated with lung diseases, PH due to chronic thrombotic and/or embolic disease (CTEPH), or PH due to miscellaneous disorders were registered. Data from adult patients included between January 1999 and December 2004 were analysed. 250 patients were registered (age 58 +/- 16 years, 104 (41%) males). 152 patients (61%) had PAH, 73 (29%) had CTEPH and 18 (7%) had PH associated with lung disease. Patients <50 years (32%) were more likely to have PAH than patients >50 years (76% vs. 53%, p <0.005). Twenty-four patients (10%) were lost to followup, 58 patients (26%) died and 150 (66%) survived without transplantation or thrombendarterectomy. Survivors differed from patients who died in the baseline six-minute walking distance (400 m [300-459] vs. 273 m [174-415]), the functional impairment (NYHA class III/IV 86% vs. 98%), mixed venous saturation (63% [57-68] vs. 56% [50-61]) and right atrial pressure (7 mm Hg [4-11] vs. 11 mm Hg [4-18]). PH is a disease affecting adults of all ages. The management of these patients in specialised centres guarantees a high quality of care. Analysis of the registry data could be an instrument for quality control and might help identify weak points in assessment and treatment of these patients.

A la recherche de symptômes de désorientation dépendant d'un déficit d'intégration multisensorielle chez l'animal : un éclairage sur les mécanismes fondamentaux de la schizophrénie

Abstract Fundamental research in psychiatric neurosciences assumes that psychiatric disorders are associated with neurobiological factors. Identification of these factors would provide therapeutic targets as well as a better understanding of the relationship between- brain and behaviour in pathological processes. We conducted experiments in an animal model of schizophrenia. Several behavioural tasks were used to evaluate spatial and working memory in these animals. The model is based on glutathione deficit during cerebral development. Indeed, a 50% decrease of glutathione has been reported in prefrontal cortex of patients with schizophrenia. Glutathione is a major antioxidant in the brain and its deficit could lead to abnormal brain connectivity. The glutathione deficit was induced in rats by perinatal (PS-P16) subcutaneous injections with Lbuthionine-(S,R)-sullfoximine (BSO), an inhibitor of glutathione synthesis. This treatment leads to a transitory 50% glutathione levels during brain development. In parallel, we conducted behavioural testing in rats with a medial prefrontal cortex lesion. This allowed us to compare early damage induced by BSO treatment with a focal lesion in adults of a brain area known to present anomalies in schizophrenia. Finally, we conducted a series of experiments in senescent rats to evaluate if cognitive deficits could be related to neurobiological changes. Our results show that an early glutathione deficit provokes cognitive deficits in adulthood. These spatial and working memory deficits resemble the cognitive deficits observed in schizophrenia. The comparison with prefrontal rats revealed that the early brain glutathione deficit provoked more severe cognitive deficits than the prefrontal lesion in adult rats. Moreover, in both cases, we observed a dissociation in memory deficits depending on the type of locomotion that was used in behavioural experiments. Indeed, BSO treated rats as well as prefrontal rats showed place learning or working memory deficits in tasks conducted on dry surfaces where they had to walk. In contrast, they showed no deficit when the same cognitive functions were tested in the water maze. This dissociation might be sustained by a difference in requirement of sensory integration between walking and swimming tasks. Résumé La recherche fondamentale en neurosciences psychiatriques repose sur le présupposé selon lequel les symptômes manifestés dans les troubles psychiatriques auraient des concomitants neurobiologiques. Ceux-ci, une fois identifiés, offriraient des cibles pour une démarche thérapeutique ainsi que des modèles permettant de mieux comprendre les soubassements biologiques du comportement et des activités mentales. Nos expériences s'articulent autour de la question de la modélisation de la schizophrénie chez l'animal. Nous avons recherché chez ces animaux des troubles cognitifs et sensoriels associés à la schizophrénie. En effet, chez l'homme comme chez l'animal, la mémoire spatiale et la mémoire de travail dépendent fortement de la capacité d'intégration et d'organisation des informations sensorielles. Les premières expériences ont été menées suite à une perturbation périnatale du développement cérébral. Celle-ci visait à reproduire une diminution du taux de glutathion dans le cerveau, des recherches précédentes ayant observé une diminution de 50% du taux de glutathion dans le cortex préfrontal de patients schizophrènes. Le glutathion étant un antioxydant majeur dans le cerveau, son déficit pourrait conduire à des perturbations de la circuiterie cérébrale. Nous avons reproduit ce déficit chez le rat, par injection de Lbuthionine-(S,R)-sullfoximine (BSO), un inhibiteur de la synthèse du glutathion... Ce traitement a été administré pendant la période périnatale (du jour postnatal 5 au jour 16) provoquant une diminution de 50% du taux de glutathion. Nous avons ensuite évalué lës répercussions de cette atteinte précoce sur le comportement des rats à l'âge adulte. Ce modèle s'inscrit donc dans l'hypothèse neurodéveloppementale qui associe la schizophrénie à une atteinte du développement cérébral normal. Nous avons ensuite conduit des expériences similaires chez des rats ayant subi une lésion du cortex préfrontal pour comparer les répercussions du traitement périnatal avec une lésion, à l'âge adulte, d'une aire cérébrale connue pour présenter des anomalies chez les patients. Finalement, nous avons évalué si les processus sensoriels et cognitifs précédemment étudiés pouvaient également être affectés lors du vieillissement normal en recherchant des corrélats biologiques des déficits de mémoire liés à l'âge avancé. Nos résultats montrent que ce déficit précoce en glutathion peut avoir des répercussions surale comportement à l'âge adulte. On a relevé une similarité avec les déficits cognitifs associés.à la schizophrénie, incluant des déficits de mémoire de travail ainsi que des déficits de mémoire spatiale. Ces déficits étaient fortement liés au type de locomotion utilisée et n'ont été observés que dans les tâches où les animaux devaient rejoindre un but en marchant mais pas dans lés tests dans lesquels ils devaient localiser une cible en nageant. Les déficits induits par la lésion préfrontale chez l'adulte étaient beaucoup plus légers que ceux découlant de l'atteinte périnatale mais présentaient une dissociation analogue en fonction du type de locomotion. De plus, des tests similaires menés au cours du vieillissement confirment que la mémoire de travail peut être affectée sélectivement par le vieillissement dans une tâche où les animaux doivent marcher, tout en restant intacte dans le bassin de Morris. Les déficits cognitifs liés au vieillissement étaient significativement corrélés à des différences de niveaux des protéines post-synaptiques PSD95 (postsynaptic density 95). L'ensemble des résultats montre que les tests qui sont fréquemment utilisés pour évaluer la mémoire chez l'animal pourraient faire appel à des processus différents. Cette différence pourrait notamment tenir au niveau d'intégration sensorielle requis pour résoudre la tâche, qui est particulièrement sollicitée au cours d'une locomotion intermittente.

A new approach to accurate measurement of uniaxial joint angles based on a combination of accelerometers and gyroscopes.

A new method of measuring joint angle using a combination of accelerometers and gyroscopes is presented. The method proposes a minimal sensor configuration with one sensor module mounted on each segment. The model is based on estimating the acceleration of the joint center of rotation by placing a pair of virtual sensors on the adjacent segments at the center of rotation. In the proposed technique, joint angles are found without the need for integration, so absolute angles can be obtained which are free from any source of drift. The model considers anatomical aspects and is personalized for each subject prior to each measurement. The method was validated by measuring knee flexion-extension angles of eight subjects, walking at three different speeds, and comparing the results with a reference motion measurement system. The results are very close to those of the reference system presenting very small errors (rms = 1.3, mean = 0.2, SD = 1.1 deg) and excellent correlation coefficients (0.997). The algorithm is able to provide joint angles in real-time, and ready for use in gait analysis. Technically, the system is portable, easily mountable, and can be used for long term monitoring without hindrance to natural activities.

Physical activity assessment using a pedometer and its comparison with a questionnaire in a large population survey.

The aim of this study was to evaluate the use of the pedometer in epidemiologic research on physical activity. Within the framework of a health examination survey in 1988-1989, physical activity was assessed in a representative population sample of 493 men and women aged 25-74 years who were residents of Switzerland. They wore a pedometer for 1 week at work and during leisure time, and the results, converted into steps per day, were compared with answers to a questionnaire. The average number of steps per day decreased from 11,900 to 6,700 and from 9,300 to 7,300 for men and women, respectively, in the youngest to the oldest age groups. For men, categorized according to type of physical activity at work, there was a highly significant difference in the number of steps (p < 0.001), whereas in women the results were associated with leisure-time physical activity (p = 0.003). For both sexes, practicing sports more than once a week was associated with an important increase in steps per day. Analyzing the number of steps according to the day of the week and occupational category produced an unexpected result: Men with a physically active job engaged in more leisure-time physical activity on the weekend. The pedometer proved to be useful in assessing physical activity in a large, free-living population.

A new way of quantifying dominant upper-limb mobility in healthy and painful shoulders

Introduction: Quantification of daily upper-limb activity is determinant in the evaluation of shoulder surgery. For a number of shoulder diseases, roblems in performing daily activities have been expressed in terms of upper-limb usage. Althought many instruments measure upper-limb movements, there is no accepted standard or widely used objective measure and no device to differenciate left or right shoulder usage. We present an objective method to measure the mobility and quantify the usage of dominant and healthy or painfull shoulder movement during daily life. Methods: 12 patients with unilateral pathological shoulder (rotator cuff disease) are compared to 18 control subjects (10 right and 8 left handed). Both SST and DASH questionnaires were completed by each one. Three inertial miniature modules including triaxial gyroscopes and accelerometers were fixed on the dorsal side of both humerus, and on the thorax. An ambulatory datalogger have recorded the signals during one day. Results: We observed that right handed healthy subjects used 18% and 26% more their dominant shoulder during respectively stand and sit postures while left handed subjects used 8% and 18% more their left side. In walking periods, shoulder mobility was quite alike for both sides. Patients affected on their dominant arm (PD group) mostly used their non-dominant side (respectively 5% and 9% during stand and sit). For the patients affected on their non-dominant shoulder (PND group), this difference is respectively 28% and 26%. Moreover, we can note that, during walking periods, a difference can be observed (on the contrary to controls). Patients used 13% and 15% more their nonpathologic side respectively for PD and PND groups. Conclusion: Inertial sensors, during long-term ambulatory monitoring of upper limbs, can quantify the difference between dominant and nondominant sides. Patients used more their non affected shoulder during daily life. For the PD group, the difference with control can be shown during walking. These results are very encouraging for future evaluation of patients with shoulder injuries since it can provide an objective evaluation of the shoulder mobility and of the treatment outcome during daily life.

Health correlates of overweight and obesity in adults aged 50 years and over: results from the Survey of Health, Ageing and Retirement in Europe (SHARE)

QUESTIONS UNDER STUDY: To examine the association between overweight/obesity and several self-reported chronic diseases, symptoms and disability measures. METHODS: Data from eleven European countries participating in the Survey of Health, Ageing and Retirement in Europe were used. 18,584 non-institutionalised individuals aged 50 years and over with BMI > or = 18.5 (kg/m2) were included. BMI was categorized into normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9) and obesity (BMI > or = 30). Dependent variables were 13 diagnosed chronic conditions, 11 health complaints, subjective health and physical disability measures. For both genders, multiple logistic regressions were performed adjusting for age, socioeconomic status and behaviour risks. RESULTS: The odds ratios for high blood pressure, high cholesterol, diabetes, arthritis, joint pain and swollen legs were significantly increased for overweight and obese adults. Compared to normal-weight individuals, the odds ratio (OR) for reporting > or = 2 chronic diseases was 2.4 (95% CI 1.9-2.9) for obese men and 2.7 (95% CI 2.2-3.1) for obese women. Overweight and obese women were more likely to report health symptoms. Obesity in men (OR 0.5, 95% CI 0.4-0.6), and overweight (OR 0.5, 95% CI 0.4-0.6) and obesity (OR 0.4, 95% CI 0.3-0.5) in women, were associated with poorer subjective health (i.e. a decreased risk of reporting excellent, very good or good subjective health). Disability outcomes were those showing the greatest differences in strength of association across BMI categories, and between genders. For example, the OR for any difficulty in walking 100 metres was non-significant at 0.8 for overweight men, at 1.9 (95% CI 1.3-2.7) for obese men, at 1.4 (95% CI 1.1-1.8) for overweight women, and at 3.5 (95% CI 2.6-4.7) for obese women. CONCLUSIONS: These results highlight the impact of increased BMI on morbidity and disability. Healthcare stakeholders of the participating countries should be aware of the substantial burden that obesity places on the general health and autonomy of adults aged over 50.

Assessment of speed of human locomotion using a differential satellite global positioning system.

PURPOSE: The objective was to explore whether a satellite-based navigation system, global positioning system used in differential mode (DGPS), could accurately assess the speed of running in humans. METHODS: A subject was equipped with a portable GPS receptor coupled to a receiver for differential corrections, while running outdoors on a straight asphalt road at 27 different speeds. Actual speed (reference method) was assessed by chronometry. RESULTS: The accuracy of speed prediction had a standard deviation (SD) of 0.08 km x h(-1) for walking, 0.11 km x h(-1) for running, yielding a coefficient of variation (SD/mean) of 1.38% and 0.82%, respectively. There was a highly significant linear relationship between actual and DGPS speed assessment (r2 = 0.999) with little bias in the prediction equation, because the slope of the regression line was close to unity (0.997). CONCLUSION: the DGPS technique appears to be a valid and inconspicuous tool for "on line" monitoring of the speed of displacement of individuals located on any field on earth, for prolonged periods of time and unlimited distance, but only in specific environmental conditions ("open sky"). Furthermore, the accuracy of speed assessment using the differential GPS mode was improved by a factor of 10 as compared to non-differential GPS.

Orofacial dysfunction in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) affects orofacial function. Our aim was to evaluate certain characteristics of orofacial function in DMD and relate possible deteriorations to the age of the patients and to the diminished internal structure quality of the masseter muscle. Bite force and finger force were measured in 16 DMD patients (6-20 years old) and 16 age matched controls. The thickness and internal structure quality of the masseter muscle were evaluated ultrasonographically. We found reduced mouth opening but no signs of masticatory muscle tenderness. Bite force values were lower for DMD patients. Masseter thickness showed no significant differences between the two groups, but poorer internal muscle structure quality characterised the elder, non-walking DMD patients explaining their low bite force values. In conclusion, the masseter muscle follows the general progress of the disease. Orofacial function in DMD patients is becoming ever more important as their life expectancy increases.

Quantitative estimation of foot-flat and stance phase of gait using foot-worn inertial sensors.

Time periods composing stance phase of gait can be clinically meaningful parameters to reveal differences between normal and pathological gait. This study aimed, first, to describe a novel method for detecting stance and inner-stance temporal events based on foot-worn inertial sensors; second, to extract and validate relevant metrics from those events; and third, to investigate their suitability as clinical outcome for gait evaluations. 42 subjects including healthy subjects and patients before and after surgical treatments for ankle osteoarthritis performed 50-m walking trials while wearing foot-worn inertial sensors and pressure insoles as a reference system. Several hypotheses were evaluated to detect heel-strike, toe-strike, heel-off, and toe-off based on kinematic features. Detected events were compared with the reference system on 3193 gait cycles and showed good accuracy and precision. Absolute and relative stance periods, namely loading response, foot-flat, and push-off were then estimated, validated, and compared statistically between populations. Besides significant differences observed in stance duration, the analysis revealed differing tendencies with notably a shorter foot-flat in healthy subjects. The result indicated which features in inertial sensors' signals should be preferred for detecting precisely and accurately temporal events against a reference standard. The system is suitable for clinical evaluations and provides temporal analysis of gait beyond the common swing/stance decomposition, through a quantitative estimation of inner-stance phases such as foot-flat.

GPS analysis of human locomotion: further evidence for long-range correlations in stride-to-stride fluctuations of gait parameters.

During free walking, gait is automatically adjusted to provide optimal mechanical output and minimal energy expenditure; gait parameters, such as cadence, fluctuate from one stride to the next around average values. It was described that this fluctuation exhibited long-range correlations and fractal-like patterns. In addition, it was suggested that these long-range correlations disappeared if the participant followed the beep of metronome to regulate his or her pace. Until now, these fractal fluctuations were only observed for stride interval, because no technique existed to adequately analyze an extended time of free walking. The aim of the present study was to measure walking speed (WS), step frequency (SF) and step length (SL) with high accuracy (<1 cm) satellite positioning method (global positioning system or GPS) in order to detect long-range correlations in the stride-to-stride fluctuations. Eight participants walked 30 min under free and constrained (metronome) conditions. Under free walking conditions, DFA (detrended fluctuation analysis) and surrogate data tests showed that the fluctuation of WS, SL and SF exhibited a fractal pattern (i.e., scaling exponent alpha: 0.5 < alpha < 1) in a large majority of participants (7/8). Under constrained conditions (metronome), SF fluctuations became significantly anti-correlated (alpha < 0.5) in all participants. However, the scaling exponent of SL and WS was not modified. We conclude that, when the walking pace is controlled by an auditory signal, the feedback loop between the planned movement (at supraspinal level) and the sensory inputs induces a continual shifting of SF around the mean (persistent anti-correlation), but with no effect on the fluctuation dynamics of the other parameters (SL, WS).

A wearable system for multi-segment foot kinetics measurement.

This study aims to design a wearable system for kinetics measurement of multi-segment foot joints in long-distance walking and to investigate its suitability for clinical evaluations. The wearable system consisted of inertial sensors (3D gyroscopes and 3D accelerometers) on toes, forefoot, hindfoot, and shank, and a plantar pressure insole. After calibration in a laboratory, 10 healthy elderly subjects and 12 patients with ankle osteoarthritis walked 50m twice wearing this system. Using inverse dynamics, 3D forces, moments, and power were calculated in the joint sections among toes, forefoot, hindfoot, and shank. Compared to those we previously estimated for a one-segment foot model, the sagittal and transverse moments and power in the ankle joint, as measured via multi-segment foot model, showed a normalized RMS difference of less than 11%, 14%, and 13%, respectively, for healthy subjects, and 13%, 15%, and 14%, for patients. Similar to our previous study, the coronal moments were not analyzed. Maxima-minima values of anterior-posterior and vertical force, sagittal moment, and power in shank-hindfoot and hindfoot-forefoot joints were significantly different between patients and healthy subjects. Except for power, the inter-subject repeatability of these parameters was CMC>0.90 for healthy subjects and CMC>0.70 for patients. Repeatability of these parameters was lower for the forefoot-toes joint. The proposed measurement system estimated multi-segment foot joints kinetics with acceptable repeatability but showed difference, compared to those previously estimated for the one-segment foot model. These parameters also could distinguish patients from healthy subjects. Thus, this system is suggested for outcome evaluations of foot treatments.

Exercice physique et artériopathie oblitérante des membres inférieurs [Physical activity and peripheral arterial obstructive disease]

Intermittent claudication (IC) is the most common clinical manifestation of atherosclerotic peripheral arterial disease. Exercise training plays a major role in treating patients with IC. Regular exercise increases functional walking capacity, reduces cardiovascular mortality and improves quality of life. This seems to be achieved by: favorable effect on cardiovascular risk factors, anti-inflammatory effect, increased collateral blood flux, improved rheology profile, endothelial function, fibrinolysis, and muscular metabolism. However, exact mechanisms underlying beneficial effect of exercise remain largely unknown. Exercise modalities will be discussed in this article.